Contribution of IL-12R mediated feedback loop to Th1 cell differentiation
Contribution of IL-12R mediated feedback loop to Th1 cell differentiation
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DOI：
10.1016/j.febslet.2007.10.007
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发表时间：
2007-11-13
期刊：
影响因子：
3.5
通讯作者：
Grusby, Michael J.
中科院分区：
文献类型：
--
作者：
Becskei, Attila;Grusby, Michael J.
辅助性T细胞1(Th1)的细胞命运是由重叠的信号通路引起的，其动力学原理和调控基序在很大程度上是未知的。我们在STAT4信号通路中发现了一个简单的正反馈环，由此被IL-12激活导致IL-12受体表达增加。计算分析表明，当Th1细胞命运诱导较弱时，这个反馈环与由分化细胞分泌的干扰素-γ介导的反馈环协同作用。正反馈环经常被用来增强表型分化。实验表明，IL-12受体基因表达的随机波动被放大，导致细胞群体中两种不同水平的表达，从而证实了这一效应。(C)2007年欧洲生化学会联合会。爱思唯尔出版公司版权所有。
T helper 1 (Th1) cell fate is induced by overlapping signaling pathways, whose kinetic principles and regulatory motifs are largely unknown. We identified a simple positive feedback loop in the STAT4 signaling pathway, whereby activation by IL-12 leads to the increased expression in IL-12 receptor. A computational analysis shows that this feedback loop synergizes with the one mediated by the IFN-gamma secreted by differentiating cells, when the induction of Th1 cell fate is weak. Positive feedback loops are often utilized to enhance phenotypic differentiation. This effect was confirmed by experiments showing that stochastic fluctuations in the expression of IL-12 receptor gene were amplified, leading to two discrete levels of expression in a cell population. (C) 2007 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.